DESCRIPTION: (Abstract from application) This proposal seeks to develop the Salisbury Eye Evaluation (SEE) Project as a population laboratory for the study of the genetics of age-related cataract, the leading cause of blindness in the world. The SEE population, now numbering 1964 subjects aged 72 years and above, has already been well characterized with regards to incidence and progression of lens opacity and known environmental and personal risk factors for cataract. The current project will continue work which has already begun to identify and examine all siblings of SEE participants living within 100 miles of Salisbury MD, estimated at greater than 1700 individuals. Lens status of the siblings will be phenotyped photographically using the Wilmer Cataract Grading System, and a sibling-pair design will be used, treating the various types of cataract as continuous outcomes, to carry out a genome-wide scan using multi-point mapping methods suitable for complex phenotypes. The current proposal requests three years of funding to accomplish the above objectives. As requested in the RFA, additional long-term goals have been established for future work in this population: follow-up photographs will be obtained on the siblings to allow determination of cataract incidence and progression rates, and loci of potential interest from the genome-wide scan will be explored in more detail using single nucleotide polymorphisms or other similar techniques.